Soy protein isolate with isoflavones does not prevent estradiol-induced endometrial hyperplasia in postmenopausal women: a pilot trial

Objective: To test the hypothesis that soy protein isolate (SPI) with isoflavones opposes the proliferative effects of exogenous estradiol (E-2) on the endometrium after menopause. Design: Thirty-nine postmenopausal women were randomized to receive daily for 6 months either 0.5 mg E-2 + placebo, 1.0 mg E-2 + placebo, 0.5 mg E-2 + 25 g SPI with 120 mg isoflavones, or 1.0 mg E-2 + 25 g SPI with 120 mg isoflavones. Primary outcome measures were endometrial histology, ultrasound endometrial thickness, and Ki67 staining quantification, a marker of cellular proliferation. Secondary outcome measures were serum lipids and markers of bone resorption. Results: Endometrial hyperplasia, endometrial stromal and epithelial cellular proliferation, and sonographically measured endometrial thickness were similarly affected in all groups. SPI did not lessen the beneficial effects of E-2 on lipids and markers of bone resorption. Conclusion: In this pilot study, SPI with isoflavones did not protect the endometrium from E-2-induced hyperplasia in postmenopausal women. If higher, long-term doses of isoflavone supplementation are found to be safe for postmenopausal women, then future studies combining E-2 with isoflavones may be feasible as an alternative to traditional hormone replacement therapy.